Influenza is a highly infectious acute respiratory disease that has plagued the human race since ancient times. It is characterized by recurrent annual epidemics and periodic major worldwide pandemics. Because of the high disease-related morbidity and mortality, direct and indirect social and economic impacts of influenza are enormous. In the past, influenza pandemics occurred every 20-25 years. It has been about thirty years since the last one. A new pandemic is considered imminent and one of the biggest challenges facing the public health systems today nationally and internationally. With recent technical progress, it has also become possible for bio-terrorists to create potential pandemic viral strains faster than natural evolution of the viruses. These threats cannot be sufficiently addressed by the currently available influenza vaccines and antiviral compounds. Therefore, a broad-spectrum therapeutics/prophylactics for influenza is critically needed. The main objective of this grant application is to create a novel class of fusion proteins capable of blocking infections by all strains of influenza viruses including pandemic viral strains. It does not need to be updated yearly and therefore can be produced readily and be available at the onset of a natural pandemic or bio-warfare. This new class of influenza therapeutics/prophylactics will also overcome the side effects and the risk of generating drug-resistant viruses associated with the current antiviral compounds. Finally, the new class of therapeutics/prophylactics will be delivered locally and topically as a nasal spray/inhalant and is expected to be safe for humans. [unreadable] [unreadable]